Clozapine and "High-Dose" Olanzapine in Refractory Early-Onset Schizophrenia: A 12-Week Randomized and Double-Blind Comparison

Sanjiv Kumra, Harvey Kranzler, Ginny Gerbino-Rosen, Hana M. Kester, Courtney DeThomas, Vivian Kafantaris, Christoph U. Correll, John M. Kane

Research output: Contribution to journalArticlepeer-review

178 Scopus citations


Background: The present study evaluated the effectiveness and safety of clozapine versus "high-dose" olanzapine in treatment-refractory adolescents with schizophrenia. Methods: Children, ages 10-18 years, who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were randomized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine (n = 18) or "high-dose" olanzapine (up to 30 mg/day) (n = 21). The primary efficacy measure was response (improvement), defined as a decrease of 30% or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of "1" (very much improved) or "2" (much improved). Results: Significantly more clozapine-treated adolescents met response criteria (66%) compared with olanzapine-treated subjects (33%). Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point. However, both treatments were associated with significant weight-gain and related metabolic abnormalities. Conclusions: This double-blind randomized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice. The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments.

Original languageEnglish (US)
Pages (from-to)524-529
Number of pages6
JournalBiological psychiatry
Issue number5
StatePublished - Mar 1 2008


  • Adolescents
  • clozapine
  • double-blind randomized clinical trial
  • olanzapine
  • schizophrenia


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